Determination of the absolute configuration of 3-pyrrolin-2-ones

Full text of DOI:10.1021/jo982151e

J . Org. Chem. 1999, 64, 2567-2570
2567
fast, universal method for the determination of the
absolute configuration. Classical methods to determine
the absolute configuration are by chemical correlation or
by the introduction of a heavy atom, followed by single-
crystal X-ray diffraction. The first method is rather time
consuming, and the second is dependent on the avail-
ability of crystals suitable for absolute configuration
determination. Recently we reported a simple circular
dichroic method for determination of the absolute con-
figuration of chiral 2(5H)-furanones.9 These butenolides
are of similar reactivity and have structural features
comparable to the 3-pyrrolin-2-ones. We have now ex-
tended the CD method to the absolute configuration
determination of 3-pyrrolin-2-ones.
Deter m in a tion of th e Absolu te
Con figu r a tion of 3-P yr r olin -2-on es
Agnes D. Cuiper,† Malgorzata Brzostowska,‡
J acek K. Gawronski,‡ Wilberth J . J . Smeets,§
Anthony L. Spek,§ Henk Hiemstra,|
Richard M. Kellogg,† and Ben L. Feringa*,†
Department of Organic and Molecular Inorganic
Chemistry, University of Groningen, Nijenborgh 4,
9747 AG Groningen, The Netherlands, Department
of Chemistry, A. Mickiewicz University,
60-780 Poznan˜, Poland, Crystal and Structural Chemistry,
Bijvoet Center for Biomolecular Research, University of
Utrecht, Padualaan 8, 3584 CH Utrecht, The Netherlands,
and Laboratory of Organic Chemistry, Institute of
Molecular Chemistry, University of Amsterdam, Nieuwe
Achtergracht 129, 1018 WS Amsterdam, The Netherlands
Received October 27, 1998
In tr od u ction
Optically active 3-pyrrolin-2-ones have been shown to
be important chiral synthons for the preparation of a
variety of biologically active compounds. These five-
membered ring lactams have successfully been used in
routes to various alkaloids1 and are suitable precursors
for unusual γ-amino acids such as statine and its
analogues.2 There are also many examples of pyrrolinone-
containing natural products with interesting pharmaco-
logical activities. Typical examples are the antitumor
alkaloid J atropham3 and the platelet aggregation inhibi-
tor PI-091.4
The chemistry of these versatile building blocks has
been explored by a number of groups. Because of their
multifunctional nature, these heterocycles can take part
in several stereoselective transformations such as con-
jugate additions,5 cycloadditions,6 acyliminium ion chem-
istry,7 and allylic substitutions.8
Resu lts a n d Discu ssion
Syn th esis. Several routes to enantiomerically pure
3-pyrrolin-2-ones 1 are reported here, and in this way
we obtained 5-alkyl-, 5-acyloxy-, and 5-alkoxypyrrolino-
nes with N-alkyl or N-acyl groups.
Route 1 is based on amino acids and provides the
N-Boc-protected 5-methyl pyrrolinone 1 (Scheme 1).2b
Following the procedure of J ouin2a further improved by
Ma2b (5S)-N-tert-butoxycarbonyl-4-hydroxy-5-methyl-3-
pyrrolin-2-one (11) was synthesized from N-Boc-protected
L-alanine and Meldrum’s acid. The synthesis of compound
2b
1 was accomplished by first reducing 11 with NaBH4
followed by elimination of the hydroxyl group of 12 via
the corresponding mesylate.10 N-Boc-protected 3-pyrrolin-
2-one 1 has been synthesized previously11 but apparently
in partly racemized form (identical NMR spectrum but
low [R]D and oil instead of solid). Compound 2 was
obtained by methylation of the hydroxy-substituted
precursor 11,2a using diazomethane, along with the
isomer 13.
Route 2 starts with a pyrrole or methoxyfuranone and
includes an enantioselective enzymatic synthesis step
(Scheme 2).12 N-Methylpyrrolinone 3 was synthesized
starting with the photooxidation of N-methylpyrrole,
followed by esterification. Subsequent enzymatic resolu-
tion by Candida antarctica-mediated transesterification
provided enantiopure 3.12
The N-acyl derivatives 4 and 5 were synthesized
starting from commercially available 5-methoxy-3-furan-
2-one and obtained enantiomerically pure by an enzy-
matic transesterification using the same lipase (C. ant-
arctica) as applied in the preparation of 3. The enzyme
specifically converted the (-)-enantiomer to the hydroxy
The increasingly frequent use of these compounds as
chiral intermediates makes it indispensable to have a
* To whom correspondence should be adressed. Feringa@chem.rug.nl.
† University of Groningen.
‡ A. Mickiewicz University.
§ University of Utrecht.
| University of Amsterdam.
(1) (a) Casiraghi, G.; Spanu, P.; Rassu, G.; Pinna, L.; Ulgheri, F. J .
Org. Chem. 1994, 59, 2906. (b) Griffart-Brunet, D.; Langois, N.
Tetrahedron Lett. 1994, 35, 119. (c) Newcombe, N. J .; Ya, F.; Vijn, R.
J .; Hiemstra, H.; Speckamp, W. N. J . Chem. Soc., Chem. Commun.
1994, 6, 767. (d) Klaver, W. J .; Hiemstra, H.; Speckamp, W. N. J . Am.
Chem. Soc. 1989, 111, 2588.
(2) (a) J ouin, P.; Castro, B. J . Chem. Soc., Perkin Trans. 1 1987,
1177. (b) Ma, D.; Ma, J .; Ding, W.; Dai, L. Tetrahedron: Asymmetry
1996, 7, 2365.
(3) Dittami, J . P.; Xu, F.; Qi, H.; Martin, M. W. Tetrahedron Lett.
1995, 36, 4201.
(4) (a) Shiraki, R.; Sumino, A.; Tadano, K.; Ogawa, S. J . Org. Chem.
1996, 61, 2845. (b) Iwasawa, N.; Maeyama, K. J . Org. Chem. 1997,
62, 1918.
(5) (a) J ime´nez, M. D.; Ortega, R.; Tito, A.; Farin˜a, F. Heterocycles
1988, 27, 173. (b) Koot, W.-J .; Hiemstra, H.; Speckamp, W. N.
Tetrahedron: Asymmetry 1993, 4, 1941.
(6) (a) Koot, W.-J .; Hiemstra, H.; Speckamp, W. N. J . Org. Chem.
1992, 57, 1059. (b) Cooper, D. M.; Grigg, R.; Hargreaves, S.; Kennewell,
P.; Redpath, J . Tetrahedron 1995, 51, 7791.
(7) Koot, W.-J .; Hiemstra, H.; Speckamp, W. N. Tetrahedron Lett.
1992, 33, 7969.
(9) Gawronski, J . K.; Oeveren van, A.; Deen van der, H.; Leung, C.
W.; Feringa, B. L. J . Org. Chem. 1996, 61, 1513.
(10) Decicco, C. P.; Grover, P. J . Org. Chem. 1996, 61, 3534.
(11) Mattern, R.-H. Tetrahedron Lett. 1996, 37, 291.
(8) Cuiper, A. D.; Kellogg, R. M.; Feringa, B. L. Chem. Commun.
1998, 655.
(12) Deen van der, H.; Cuiper, A. D.; Hof, R. P.; Oeveren van, A.;
Feringa, B. L.; Kellogg, R. M. J . Am. Chem. Soc. 1996, 118, 3801.
10.1021/jo982151e CCC: $18.00 © 1999 American Chemical Society
Published on Web 03/11/1999

2568 J . Org. Chem., Vol. 64, No. 7, 1999
Sch em e 1. Syn th esis of 3-P yr r olin -2-on es
Notes
Sch em e 2. Syn th esis of 3-P yr r olin -2-on es
Sch em e 3. Syn th esis of 3-P yr r olin -2-on es
Sch em e 4. Syn th esis of P yr r olin on e Ir on
derivative 14, and the unreactive (+)-enantiomer was
obtained in >99% ee. In this way the maximum yield of
50% of enantiopure product in a kinetic resolution was
obtained.12 Compounds 6-8 were obtained by the reverse
reaction, the enzymatic esterification of hydroxypyrroli-
none 14. In this reaction the (-)-enantiomer of 14 was
converted to the (-)-acyloxypyrrolinones 6-8. Because
the hydroxypyrrolinone 14 racemized under the reaction
conditions, 6-8 could be obtained enantiomerically pure
in quantitative yield by a dynamic kinetic resolution.12
The 5-isopropoxy pyrrolinones 9 and 10 were obtained
via a stereoselective synthesis route,6a,13 starting with (S)-
malic acid (Scheme 3).
Tetr a ca r bon yl Com p lexes
A method to establish independently the absolute
configuration of 3-pyrrolin-2-ones is via synthesis and
characterization of the corresponding iron tetracarbonyl
complexes (Scheme 4). By reaction with Fe2(CO)9 pyr-
rolinone, (+)-5 was converted into a 1:1 mixture of cis-
(15a ) and trans-(15b) Fe(CO)4 complexes (Scheme 4). The
lack of π-face selectivity is in contrast with the selectivity
observed in our synthesis of iron complexes with isopro-
poxy-substituted pyrrolinones13,14 (in which case the cis
complex is formed predominantly, probably because of
precoordination of iron to the oxygen atom of the isopro-
poxy group). The isomers were distinguished on the basis
of the coupling constants between H(4) and H(5) in the
1H NMR spectra. For the cis complex 15a a value of 5
Hz was found, whereas for the trans complex 15b J <
0.5 Hz was observed. As in other pyrrolinone iron
tetracarbonyl complexes,13,14 the C(3)-C(4) bond is elon-
gated from about 1.3 Å for a normal double bond to 1.414
(5) Å in the complex.
(13) Hopman, J . C. P.; Hiemstra, H.; Speckamp, W. N. Chem.
Commun. 1995, 617.
(14) Koot, W.-J .; Hiemstra, H.; Speckamp, W. N. Chem. Commun.
1993, 156.

Notes
J . Org. Chem., Vol. 64, No. 7, 1999 2569
Ta ble 1. CD a n d UV Da ta for Ch ir a l 3-P yr r olin -2-on es
(in Aceton itr ile)
F igu r e 1. Correlation of the pyrrolinone Cotton effects with
absolute configuration.
CD, ∆ꢀ (nm)/UV, ꢀ (nm)
R,â unsaturated lactam
com-
other CD
bands
associated with the R,â-unsaturated lactam chromophore
(Figure 1). This is an extension of the configurational rule
previously developed for R,â-unsaturated lactones (2(5H)-
furanones).9 The extension is justified in view of the
planarity of the R,â-unsaturated lactam ring, as demon-
strated by the published X-ray data (vide infra),6a,16 and
by the isoelectronic nature of the unsaturated chro-
mophore in 3-pyrrolin-2-ones and in 2(5H)-furanones.
The most easy and reliable assignment of absolute
configuration is based on the sign of the π-π* Cotton
effect (identified by the position of the UVmax): positive
π-π* Cotton effect is due to P-helicity of the CdC-C-
R1 bond system; negative π-π* Cotton effect reflects
M-helicity of the same bond system. Although no detailed
discussion of the observed relationship is offered here,
we note that coupling of the π-π* electric dipole transi-
tion moment of the planar (conjugated) chromophore with
the σ* oscillator of the allylic carbon-carbon or carbon-
heteroatom bond is quite a well-established mechanism
of generating the rotational power.17
pound
R1
Me
R2
R3
n-π*
π-π*
1
2
Boc
H
-0.8 (224)
+7.8 (200)
5300 sh (226) 9900 (205)
Me
Boc
Me
MeO -0.8 (251)
+2.8 (229)
12200 (228)
+25 (198)
a
3
AcO
H
H
H
H
H
H
H
H
-6 (250)
3400 sh (232)
-8.5 (230) +30.6 (206) -0.6 (280)
4
EtCOO EtCO
3600 sh (228) 10500 (203)
-9.6 (230)
3900 sh (228) 9600 (205)
+9.7 (230)
3600 sh (227) 10100 (203)
+9.0 (230)
3400 sh (228) 9800 (203)
+8.8 (230)
3400 sh (228) 9500 (204)
+6 (236)
2000 sh (235)
+1.8 (271)
5
AcO
AcO
AcO
Ac
+28.1 (206) -0.6 (280)b
6
Ac
-28.9 (205) +0.9 (280)
7
EtCO
-30.0 (206) +0.6 (280)
8
EtCOO Ac
-31.0 (206) +0.6 (280)
9
i-PrO
i-PrO
Ac
Ts
-20 (212)
a
-6.0 (233)
12100 (229)
+1.0 (279)
-1.8 (256)
10
a
No clear λmax down to 200 nm. b Recorded in methanol solution.
Inspection of [R]D data in the literature for chiral
3-pyrrolin-2-ones6a,13,16,18 reveals that the sign of [R]D,
with apparently no exception, corresponds to the sign of
the π-π* R,â-unsaturated lactam CD band: that is,
positive [R]D results from the contribution of the (strong)
positive π-π* Cotton effect. Thus the sign of rotation of
3-pyrrolin-2-ones can be used for tentative assignment
of its absolute configuration at C(5), but this assignment
needs to be confirmed by the measurement of the CD
spectrum.
Absolu te Con figu r a tion by Ch em ica l Cor r ela tion
a n d X-r a y An a lysis. The compounds 1 and 2 were
synthesized starting from enantiopure L-alanine and
should therefore have the (S)-configuration. The synthe-
sis of the pyrrolinones 9 and 10 from enantiopure (S)-
malic acid could only yield the (R)-enantiomer. This
correlates with the absolute configuration of the iron
tetracarbonyl complex of 10 recently reported by some
of us.13 For the compounds 3-8 there is no chemical
correlation because these compounds were synthesized
from an achiral or racemic starting material. For com-
pound 5 the absolute configuration could be deduced from
the crystal structure of the iron tetracarbonyl complex.
The synthesis of this complex has been described
The cis-isomer could not be isolated in pure form and
was obtained by flash chromatography under nitrogen
either as a mixture with the trans-isomer or contami-
nated with the starting material.
Pure trans-isomer 15b was isolated by flash chroma-
tography and recrystallized from pentane to give suitable
crystals for X-ray crystal structure determination. The
crystalline complex is stable to air.
CD Stu d ies. In the case of simple 3-pyrrolin-2-ones
bearing no substituents at the olefinic bond, the π-π*
Cotton effect is observed at λmax ca. 200 nm. The n-π*
Cotton effect is seen at longer wavelength, around 230
nm, where the UV spectrum displays a broad shoulder.
CD/UV spectral data of all pyrrolinones investigated are
shown in Table 1.
The 3-pyrrolin-2-ones with an oxygen substituent at
C(5) generally display much stronger Cotton effects than
those substituted with an alkyl group (e.g., compounds
1, 2). A methoxy substituent at C(3) shifts the position
of the π-π* band to ca. 230 nm (compound 2), as does
tosyl substitution at N(1) (compound 10).
3-Pyrrolin-2-ones with an imide-type group (R2 ) acyl)
display an additional Cotton effect at ca. 280 nm,
presumably due to a second n-π* transition. Such double
n-π* Cotton effects are observed at ca. 250 nm in
saturated imides15 and result from the transitions involv-
ing combinations of the carbonyl n orbitals of opposite
symmetry. This Cotton effect is, however, much smaller
than the n-π* Cotton effect due to the R,â-unsaturated
lactam chromophore.
(16) Rassu, G.; Casiraghi, G.; Spanu, P.; Pinna, L.; Fava, G. G.;
Ferrari, M. B.; Pelosi, G. Tetrahedron: Asymmetry 1992, 3, 1035.
(17) Gawronski, J . K. In Houben-Weyl Methods of Organic Chem-
istry, 4th ed.; G. Thieme: Stuttgart, 1995; Vol. E21a, pp 499-533.
(18) (a) Soro, P.; Rassu, G.; Spanu, P.; Pinna, L.; Zanardi, F.;
Casiraghi, G. J . Org. Chem. 1996, 61, 5172. (b) Zanardi, F.; Battistini,
L.; Nespi, M.; Rassu, G.; Spanu, P.; Cornia, M.; Casiraghi, G.
Tetrahedron: Asymmetry 1996, 7, 1167. (c) Baussanne, I.; Royer, J .
Tetrahedron Lett. 1996, 37, 1213. (d) Rassu, G.; Pinna, L.; Spanu, P.;
Ulgheri, F.; Cornia, M.; Zanardi, F.; Casiraghi, G. Tetrahedron 1993,
49, 6489. (e) Rassu, G.; Zanardi, F.; Cornia, M.; Casiraghi, G. J . Chem.
Soc., Perkin Trans. 1 1994, 2431. (f) Ikota, N. Chem. Pharm. Bull. 1992,
40, 1925.
The absolute configuration of chiral 3-pyrrolin-2-ones
is readily determined by the sign of the Cotton effects
(15) Polonski, T.; Milewska, M. J .; Gdaniec, M.; Gilski, M. J . Org.
Chem. 1993, 58, 3134, and references therein.

2570 J . Org. Chem., Vol. 64, No. 7, 1999
Notes
) 0.5, MeOH). 1H NMR (CDCl3, 300 MHz), major diastere-
omer: δ 1.33 (d, 3H, J ) 6.5 Hz), 1.53 (s, 9H), 2.24 (br, s, 1H),
2.58 (dd, 1H, J ) 17.1, 8.9 Hz), 2.72 (dd, 1H, J ) 17.1, 7.5 Hz),
4.25 (dq, 1H, J ) 6.5, 6.5 Hz), 4.51 (dd, 1H, J ca. 7.5 Hz). IR
(KBr): 3479, 2986, 2931, 1767, 1685 cm-1
.
5(S)-N-ter t-Bu toxycar bon yl-5-m eth yl-3-pyr r olin -2-on e (1).
The compound has mp 73-74 °C; [R]D +145 (c ) 1, CHCl3) (lit.8
colorless oil, [R]D -9.6, c ) 1, CHCl3). 1H NMR (CDCl3, 300
MHz): δ 1.44 (d, 3H, J ) 6.7 Hz), 1.56 (s, 9H), 4.62 (dq, 1H, J
) 6.7, 1.8 Hz), 6.07 (dd, 1H, J ) 6.1, 1.8 Hz), 7.10 (dd, 1H, J )
6.1, 2.1 Hz). IR (KBr): 3076, 2985, 1765, 1688 cm-1
.
5(S)-N-ter t-Bu toxyca r bon yl-4-m eth oxy-5-m eth yl-3-p yr -
r olin -2-on e (2). Oil; [R]D +13.3 (c ) 1, CHCl3). 1H NMR (CDCl3,
300 MHz): 1.47 (d, 3H, J ) 6.6 Hz), 1.54 (s, 9H), 3.83 (s, 3H),
4.38 (q, 1H, J ) 6.6 Hz), 5.03 (s, 1H). IR (neat): 2960, 2873,
1729 cm-1
.
5(S)-N-ter t-Bu toxyca r bon yl-2-m eth oxy-5-m eth yl-2-p yr -
r olin -4-on e (13). The compound has mp 62-64 °C; [R]D -12.7
1
(c ) 0.5, CHCl3). H NMR (CDCl3, 300 MHz): 1.49 (d, 3H, J )
6.9 Hz), 1.53 (s, 9H), 4.02 (s, 3H), 4.09 (q, 1H, J ) 6.9 Hz); 4.86
(s, 1H); IR (KBr): 2932, 2860, 1778, 1630 cm-1
.
[5(S)-Acetic Acid 1-Acetyl-5-oxo-2,5-d ih yd r o-1H-p yr r ol-
2-yl Ester ] Tetr a ca r bon yl Ir on (15). To a suspension of (+)-5
(1.00 g, 5.46 mmol) in diethyl ether (60 mL) was added Fe2(CO)9
(4.00 g, 11.00 mmol), and the reaction mixture was stirred at
room temperature for 20 h. The mixture was filtered over Celite
(under an Ar atmosphere, using a connecting filter) and washed
with 20 mL of diethyl ether. The dark green solution was
concentrated in vacuo, using a rotary evaporator equipped with
a nitrogen inlet. The crude product was purified using flash
chromatography under nitrogen pressure (pet. ether/CH2Cl2/
EtOAc 5:5:2). Dry degassed solvents and silica were used, and
fractions were maintained under argon. Pure crystalline 15b,
0.363 g (1.03 mmol, 19%, Rf 0.45), was obtained and recrystal-
lized from pentane to provide light yellow prisms, mp 100 °C
(dec). 1H NMR (CDCl3, 200 MHz): δ 2.12 (s, 3H), 2.43 (s, 3H),
3.68 (d, J ) 5.4 Hz, 1H), 3.87 (d, J ) 5.1 Hz, 1H), 6.78 (s, 1H).
13C NMR (CDCl3, 50.32 MHz): δ 20.9 (q), 24.6 (q), 43.6 (d), 51.2
(d), 84.2 (d), 205.7 (s). Anal. Calcd for C12H9NO8Fe: C 41.06, H
2.58, N 3.99, Fe 15.91. Found: C 41.25, H 2.60, N 4.01, Fe 15.70.
A mixture of 15b and 15a (0.667 g, 1.90 mmol, 35%) was
obtained as a yellow solid, and a mixture of 0.382 g of 15a and
5 (6:4 ratio) was obtained as a light brown solid.
F igu r e 2. ORTEP drawing (50% probability ellipsoids) of 15b.
above.The crystal and molecular structure of 15b is
shown in Figure 2. This establishes the trans-relative
configuration of the complex as well as the (S)-absolute
configuration at C(5). From the structure of this complex
the absolute configuration at C(5) of the (+)-pyrrolinone
5 that was used can be unequivocally assigned to be S
in accordance with the assignment according to CD.
Con clu sion
By correlation of the sign of CD Cotton effects (Figure
1, Table 1) the absolute configurations of 1-10 are
established. Since the results from the chemical correla-
tion or X-ray crystal structure determination for a
compound in each of the three classes of chiral pyrroli-
nones correlate perfectly with the absolute configurations
determined by the sign of the Cotton effects for all studied
pyrrolinones, we can conclude that CD measurement is
both a rapid and a reliable method to obtain the absolute
configuration of chiral 3-pyrrolin-2-ones.
For 15a : 1H NMR (CDCl3): δ 2.11 (s, 3H), 2.41 (s, 3H), 3.89
(d, J ) 5.6 Hz, 1H), 4.26 (dd, J ) 5.1 Hz, 1H), 6.89 (d, J ) 4.6
Hz, 1H).
Cr ysta l Da ta for 15b. C12H9NO8Fe, orthorhombic, space
group P212121, a ) 7.2818(11) Å, b ) 10.0953(14) Å, c )
19.1003(17) Å, V ) 1404.1(3) Å3, Z ) 4, Mo KR, λ ) 0.710 73 Å,
µ ) 1.1 mm-1. X-ray data were collected on an Enraf-Nonius
CAD4T diffractometer (rotating anode, graphite monochromator,
T ) 150 K, θmax ) 27.5°). The structure was solved with
Patterson techniques using DIRDIF96 and refined by full-matrix
least-squares on F2 using SHELXL97 (1918 reflections and 218
parameters). A final difference map showed no significant
residual density. Hydrogen atoms of the methyl moieties were
refined as rigid rotators riding on their carrier atoms. All other
H atoms were located from a difference map and their positions
refined. Convergence was reached at R ) 0.0365 for 1918
reflections with I > 2σ(I) [wR2 ) 0.0890, S ) 1.04]. The Flack
parameter converged to 0.00(3) for the absolute configuration
shown in Figure 2. Full details are available in the Supporting
Information.
Exp er im en ta l Section
Gen er a l In for m a tion . The CD spectra were recorded with
a J obin-Yvon Dichrograph III, and the UV spectra were obtained
on a Shimadzu UV 160 spectrophotometer. Optical rotations
were determined with a Perkin-Elmer 241 polarimeter. Melting
1
points are uncorrected. Chemical shifts of the H NMR and 13C
NMR spectra are denoted in δ-units (ppm) relative to CDCl3.
The splitting patterns are designated as follows: s (singlet), d
(doublet), dd (double doublet), t (triplet), q (quartet), m (mul-
tiplet), and br (broad). Rf values were obtained by using TLC
on silica gel-coated plastic sheets (Merck silica gel F254). Merck
silica gel 60 (230-400 mesh) was used for filtration and for flash
chromatography. The solvents were distilled and dried, if
necessary, using standard methods. Reagents were used as
obtained from Acros Chimica, Aldrich, Fluka, or Merck, unless
otherwise stated.
Ack n ow led gm en t. A.D.C. is supported by the pro-
gram Innovative Research in Catalysis, an activity of
the Dutch Ministry of Economic Affairs. A.L.S and
W.J .J .S are supported by the Dutch National Science
Foundation, administered through the Office for Chemi-
cal Research.
Pyrrolinones 3-812 and 9,6a 1013 were prepared following
reported procedures.
5(S)-N-ter t-Bu t oxyca r b on yl-4-h yd r oxy-5-m et h yl-3-p yr -
r olin -2-on e (11). 11 was synthesized following the procedure
of J ouin2a and further improved by Ma.2b Compound 11 has mp
122-124 °C; [R]D +77.8 (c ) 1, MeOH). 1H NMR (CDCl3, 300
MHz): δ 1.51 (d, 3H, J ) 6.9 Hz), 1.56 (s, 9H), 3.23 (m, 2H),
4.42 (dq, 1H, J ) 6.9, 1.0 Hz), 5.00 (s, 1H). IR (KBr): 3419, 2976,
Su p p or tin g In for m a tion Ava ila ble: Tables of X-ray
crystallographic data. This material is available free of charge
via the Internet at http://pubs.acs.org.
1718, 1678, 1568 cm-1
.
5(S)-N-ter t-Bu toxyca r bon yl-4-h yd r oxy-5-m eth ylp yr r oli-
d in e-2-on e (12). The compound has mp 85-87 °C; [R]D +48 (c
J O982151E